Fire ants, (Solenopsis spp.) are a pest of economic and medical significance in the United States in part due to the painful, and sometimes dangerous, sting they inflict. We have demonstrated histamine release from rat mast cells in vitro by venoms of two species of fire ants, Solgenopsis invicta and S. geminata. This histamine releasing activity correlates with estimations of the relative toxicities of the two venoms in vivo. We have also shown that a synthetic piperidine, cis-2-methyl-6-n-undecylpiperidine, which is a component of several fire ant venoms, also causes histamine release. Histamine and lactic acid dehydrogenase (LDH) a cytoplasmic enzyme, are released concurrently, indicating disruption of the plasma membrane by the venoms and their piperidine components. We propose to determine the extent to which the piperidine components of the venom are responsible for the effects of fire ant stings, to investigate whether the antimicrobial activity of the venom is also due to membrane disruption, to synthesize additional venom piperidines and related compounds and study their structure-activity relations for histamine- and LDH-release from mast cells, antimicrobial and enzyme releasing activity in microorganisms, and hemolysis of red blood cells. More detailed understanding of the interaction of these agents with the membrane will be obtained through electron spin resonance and scanning electron microscope studies of red blood cell membranes in the presence and absence of the venoms and piperidines.